Die Entwicklung der Kommunalen Selbstverwaltung zwischen Politikverfl echtung und politischer Dezentralisierung

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Regulierung der Armut durch bürgerschaftliche Sozialpolitik: zur Programmatik einer (volks-)gemeinschaftlichen Armutsbekämpfung im Rahmen einer radikalisierten Standortpolitik

Offiziell sind freiwillige Aktivitäten im Bereich des gemeinwohlorientierten Wirtschaftens zulässig und sollen ergänzenden Charakter haben. Da diese Form von Arbeit faktisch ausschließlich im sozialen Dienstleistungsbereich angesiedelt ist, erfüllt sie nur selten das Kriterium, eine ergänzende Arbeit darzustellen. Häufig wird vorhandene Arbeit durch die Engagementarbeit - sei es die von Transferempfängern oder von Freiwilligen - substituiert. Dadurch entsteht im sozialen Dienstleistungsbereich - einem sich zur Sozialwirtschaft wandelnden Arbeitsmarkt - ein staatlich subventionierter Niedriglohnsektor, der auch Druck auf die professionellen Fachkräfte ausübt: ihnen wird demonstriert, dass sich zunehmend mehr Tätigkeitsmerkmale ihrer Arbeit auch durch Engagement ersetzen lassen. Engagementpolitik schafft so einen zunehmend wachsenden Kreis von arbeitenden Engagierten, die Teil des neuen Reservearmeemechanismus werden, auch wenn sie bereits aus dem Erwerbsleben ausgeschieden sind, wie bspw. die aktivierten Senioren. Engagement erlaubt es, in ausgewählten Bereichen professionelle Hilfe zu substituieren. So erhält der "Gebrauchswert" der Engagierten auch darin eine Funktion, Druck auf den "Tauschwert" der Professionellen auszuüben, und unterstützt auf diese Weise den Tatbestand, dass soziale Dienste "unter Wert" bezahlt werden. (ICB2

Discovery and Characterization of ORM‐11372, a Novel Inhibitor of the Sodium‐Calcium Exchanger with Positive Inotropic Activity

Background and purpose The lack of selective sodium‐calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1. inhibitor. Experimental approach A flavan series‐based pharmacophore model was constructed. Virtual screening helped us identify a novel scaffold for NCX inhibition. A distinctively different NCX 1.1 inhibitor, ORM‐11372, was discovered after lead optimization. Its potency against human and rat NCX 1.1 and selectivity against other ion channels was assessed. The cardiovascular effects of ORM‐11372 were studied in normal and infarcted rats, and rabbits. Human cardiac safety was studied ex‐vivo using human ventricular trabeculae. Key results ORM‐11372 inhibited human NCX 1.1 reverse and forward currents; IC50 values were 5 and 6 nM, respectively. ORM‐11372 inhibited human cardiac sodium 1.5 (INa) and hERG KV11.1 currents (IhERG) in a concentration‐dependent manner; IC50 values were 23.2 and 10.0 μM. ORM‐11372 caused no changes in action potential duration; short term variability and triangulation were observed for concentrations of upto 10 μM. ORM‐11372 induced positive inotropic effects in 18 ± 6% and 35 ± 8% anesthetized rats with myocardial infarctions and rabbits, respectively; no other haemodynamic effects were observed, except improved relaxation at the lowest dose. Conclusion and implications ORM‐11372, a unique, novel, and potent inhibitor of human and rat NCX 1.1, is a positive inotropic compound. NCX inhibition can induce clinically relevant improvements in left ventricular contractions without affecting relaxation, heart rate, or blood pressure, without pro‐arrhythmic risk

Discovery and characterization of ORM-11372, a novel inhibitor of the sodium-calcium exchanger with positive inotropic activity

BACKGROUND AND PURPOSE: The lack of selective sodium-calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1 inhibitor. EXPERIMENTAL APPROACH: A flavan series-based pharmacophore model was constructed. Virtual screening helped us identify a novel scaffold for NCX inhibition. A distinctively different NCX 1.1 inhibitor, ORM-11372, was discovered after lead optimization. Its potency against human and rat NCX 1.1 and selectivity against other ion channels was assessed. The cardiovascular effects of ORM-11372 were studied in normal and infarcted rats and rabbits. Human cardiac safety was studied ex vivo using human ventricular trabeculae. KEY RESULTS: ORM-11372 inhibited human NCX 1.1 reverse and forward currents; IC(50) values were 5 and 6 nM respectively. ORM-11372 inhibited human cardiac sodium 1.5 (I(Na) ) and hERG K(V) 11.1 currents (I(hERG) ) in a concentration-dependent manner; IC(50) values were 23.2 and 10.0 μM. ORM-11372 caused no changes in action potential duration; short-term variability and triangulation were observed for concentrations of up to 10 μM. ORM-11372 induced positive inotropic effects of 18 ± 6% and 35 ± 8% in anaesthetized rats with myocardial infarctions and in healthy rabbits respectively; no other haemodynamic effects were observed, except improved relaxation at the lowest dose. CONCLUSION AND IMPLICATIONS: ORM-11372, a unique, novel, and potent inhibitor of human and rat NCX 1.1, is a positive inotropic compound. NCX inhibition can induce clinically relevant improvements in left ventricular contractions without affecting relaxation, heart rate, or BP, without pro-arrhythmic risk.Peer reviewe

Multi-scale transport and exchange processes in the atmosphere over mountains. Programme and experiment

TEAMx is an international research programme that aims at improving the understanding of exchange processes in the atmosphere over mountains at multiple scales and at advancing the parameterizations of these processes in numerical models for weather and climate prediction–hence its acronyms stands for Multi-scale transport and exchange processes in the atmosphere over mountains – Programme and experiment. TEAMx is a bottom-up initiative promoted by a number of universities, research institutions and operational centres, internationally integrated through a Memorandum of Understanding between inter- ested parties. It is carried out by means of coordinated national, bi-national and multi-national research projects and supported by a Programme Coordination Office at the Department of Atmospheric and Cryospheric Sciences of the University of Innsbruck, Austria. The present document, compiled by the TEAMx Programme Coordination Office, provides a concise overview of the scientific scope of TEAMx. In the interest of accessibility and readability, the document aims at being self-contained and uses only a minimum of references to scientific literature. Greyboxes at the beginning of chapters list the literature sources that provide the scientific basis of the document. This largely builds on review articles published by the journal Atmosphere between 2018 and 2019, in a special issue on Atmospheric Processes over Complex Terrain. A few other important literature pieces have been referenced where appropriate. Interested readers are encouraged to examine the large body of literature summarized and referenced in these articles. Blue boxes have been added to most sub-chapters. Their purpose is to highlight key ideas and proposals for future collaborative research

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe